Methods and Applications of Multivariate Pattern Analysis in Functional MRI Data Analysis.

In spite of the tremendous advances in science and technology, the human brain and its functions are still not completely understood. Functional magnetic resonance imaging (fMRI) is an imaging modality that allows for non-invasive study of brain function and physiology. Thus, fMRI has found many applications in various fields involved in the study of cognition, psychology, psychiatry, neuroscience, etc. Machine learning techniques have gained tremendous interest in recent times for fMRI data analysis. These methods involve learning from numerous examples and then making predictions for new unseen examples. This work addresses the use of machine learning techniques to find and study multivariate patterns in the fMRI brain data. The two main applications explored in this work include temporal brain-state prediction and subject categorization. The within-subject brain-state prediction setup has been used to compare and contrast three different acquisition techniques in a motor-visual activation study. It has also been implemented to highlight the differences in pain regulation networks in healthy controls and subjects with temporomandibular disorders. Lastly, regression has been used to predict graded fMRI activation on a continuous scale in a motor activation and craving study. The between-subject categorization setup has been used to distinguish between patients with Asperger's disorder and healthy controls. A major contribution of our work involves a novel multi-subject machine learning framework. This technique helps to learn a model which is based on information acquired from multiple other subjects' data in addition to the subject's own data. This has been used to classify the craving and non-craving brain states of nicotine-dependent subjects, allowing examination of both population-wide as well as subject-specific neural correlates of nicotine craving. A real-time neurofeedback setup was implemented to provide feedback to a subject using their own brain activation data. Subjects can then be trained to self-regulate their own brain activation.PhDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/111357/1/ysshah_1.pd

Development and validation of dissolution method for carvedilol compression-coated tablets

The present study describes the development and validation of a dissolution method for carvedilol compression-coated tablets. Dissolution test was performed using a TDT-06T dissolution apparatus. Based on the physiological conditions of the body, 0.1N hydrochloric acid was used as dissolution medium and release was monitored for 2 hours to verify the immediate release pattern of the drug in acidic pH, followed by pH 6.8 in citric-phosphate buffer for 22 hours, to simulate a sustained release pattern in the intestine. Influences of rotation speed and surfactant concentration in medium were evaluated. Samples were analysed by validated UV visible spectrophotometric method at 286 nm. 1% sodium lauryl sulphate (SLS) was found to be optimum for improving carvedilol solubility in pH 6.8 citric-phosphate buffer. Analysis of variance showed no significant difference between the results obtained at 50 and 100 rpm. The discriminating dissolution method was successfully developed for carvedilol compression-coated tablets. The conditions that allowed dissolution determination were USP type I apparatus at 100 rpm, containing 1000 ml of 0.1N HCl for 2 hours, followed by pH 6.8 citric-phosphate buffer with 1% SLS for 22 hours at 37.0 ± 0.5 ºC. Samples were analysed by UV spectrophotometric method and validated as per ICH guidelines.O presente estudo descreve o desenvolvimento e a validação de método de dissolução para comprimidos revestidos de carvedilol. O teste de dissolução foi efetuado utilizando-se o aparelho para dissolução TDT-06T. Com base nas condições fisiológicas do organismo, utilizou-se ácido clorídrico 0,1 N como meio de dissolução e a liberação foi monitorada por 2 horas para se verificar o padrão de liberação imediata do fármaco em condições de pH baixo, seguidas por pH 6,8 em tampão cítrico-fosfato por 22 horas, para simular o padrão de liberação controlada no intestino. Avaliou-se a influência da velocidade de rotação e a concentração de tensoativo no meio. As amostras foram analisadas por método espectrofotométrico UV-visível validado, em 286 nm. O laurilsulfato sódico a 1% (SLS) mostrou-se ótimo para aumentar a solubilidade do carvedilol em pH 6,8 em tampão cítrico-fosfato. A análise da variância não mostrou diferença significativa entre os resultados obtidos a 50 e a 100 rpm. O método da dissolução discriminante foi desenvolvido com sucesso para os comprimidos revestidos de carvedilol. As condições que permitiram a determinação da dissolução foram: aparelho USP tipo I a 100 rpm, contendo 1000 mL de HCL 0,1 N por 2 horas, seguido de pH 6,8 com tampão cítrico-fosfato, com 1% de SLS por 22 horas a 37,0 ± 0,5 ºC. Amostras foram analisadas por método espectrofotométrico e validadas pelas normas ICH

The Relationship Between Smartphone Addiction and Neck Pain Prevalence among Older Population: A Cross Sectional Study

Introduction: After pandemics of covid 19, world interaction has been more through social media and through virtual. With lots of benefit of the technology, there is a pitfall of this also. Because of this, usage of smart phone has increased so addiction of it occurs even in elderly population. Due to their posture of using smart phone, and its addiction, there may be chances of having additional neck pain and disabilities. So, here is the need to see whether their smart phone addiction has any role in their neck pain prevalence. Methodology: The study examined 90 elderly population from Ahmedabad by random table sampling, in the age group of 60-70 years. Participants were asked to fill a Performa with the questionnaires of smart phone addiction scale (SAS) and neck disability index (NDI). Level of significant was kept at 5%. Spearman correlation coefficient was used to correlate between both SAS and NDI. Result: From 90 participants, there was 36 females and 54 males. Mean±SD of SAS and NDI was 107.8±22.5 and 7.4±4.99 respectively. Spearman correlation coefficient showed a significant Moderate positive correlation between SAS and NDI (r=0.649, p<0.001). Conclusion: The study showed the positive correlation between smartphone addiction and musculoskeletal problems in neck in elderly population

The Role of Hoxd10 in the Development of the Motoneurons in the Posterior Spinal Cord

Hox genes encode anterior-posterior identity during central nervous system development. Few studies have examined Hox gene function at lumbosacral (LS) levels of the spinal cord, where there is extensive information on normal development. Hoxd10 is expressed at high levels in the embryonic LS spinal cord, but not the thoracic (T) spinal cord. To test the hypothesis that restricted expression of Hoxd10 contributes to the attainment of an LS identity, and specifically an LS motoneuron identity, Hoxd10 was ectopically expressed in T segments in chick embryos via in ovo electroporation. Electroporations were carried out at early neural tube stages (stages 13-15) and at the onset of motoneuron differentiation (stages 17-18). Regional motoneuron identity was assessed after the normal period of motor column formation (stages 28-29). Subsets of motoneurons in transfected T segments developed a molecular profile normally shown by anterior LS LMCl motoneurons, including Lim 1 and RALDH2 expression. In addition, motoneurons in posterior T segments showed novel axon projections to two muscles in the anterodorsal limb, the sartorius and anterior iliotibialis muscles. These changes are accompanied by a significant reduction in the number of T motoneurons at stage 29. Analyses of Hoxd10 electroporated embryos at the onset of motor column formation (stage 18) suggest that early and high levels of Hoxd10 expression led to the death of some early differentiating motoneuron. Despite these adverse effects, our data indicate that Hoxd10 expression is sufficient to induce LS motoneuron identity and axon trajectories characteristic of motoneurons in the LS anterior spinal cord. Equivalent changes in motoneuron identity were not found with the ectopic expression of Hoxd9, a gene normally expressed in T as well as LS segments. In an additional series of experiments, Hoxd10 was overexpressed in LS segments via in ovo electroporation at early neural tube stages. Analyses at stage 29 indicated proportionate increases in LMCl (Lim 1+, RALDH2+) motoneurons, and proportionate decreases in LMCm and MMC motoneurons (Isl 1+) motoneurons. These findings suggest that Hoxd10 specifically promotes the development and/or survival of LMCl motoneurons

Surgical Treatment of Liver Metastases in Neuroendocrine Neoplasms

Neuroendocrine neoplasms (NENs) are a distinctive entity, and nearly 10% of patients already have liver metastases at presentation. The management of neuroendocrine liver metastases (NEN-LM) is complex with differing patterns of metastatic presentation. An aggressive approach should be used to resect the primary tumor, to remove regional lymph nodes, and to resect or treat appropriate distant metastases (including liver tumors). Despite having an indolent course, NENs have a significantly reduced survival when liver metastases are untreated. Though a wide range of therapies are now available with a multimodal approach to the treatment, surgical treatment offers the only chance for a significant survival prolongation and/or improvement of symptoms and quality of life. A review of the existing surgical modalities for NEN-LM is discussed in this paper

Modulation of Intestinal Micrornas by a Chemoprotective Diet

We have hypothesized that dietary modulation of intestinal miRNA expression may contribute to the chemoprotective effects of nutritional bioactives (fish oil and pectin). Using a rat colon carcinogen model, we determined miRNAs-let-7d, miR-15b, miR-107, miR-191 and miR-324-5p were modulated by fish oil + pectin. We also demonstrated that BACE1 and PTEN are targets of miR-107 and miR-21, respectively. To further elucidate the biological effects of diet and carcinogen on miRNAs, we integrated global miRNAs, total and polysomal gene expression datasets obtained from the above mentioned study and used four computational approaches. We demonstrated that polysomal profiling is tightly related to microRNA changes when compared with total mRNA profiling. In addition, diet and carcinogen exposure modulated a number of microRNAs and complementary gene expression analyses showed that oncogenic PTK2B, PDE4B, and TCF4 were suppressed by the chemoprotective diet at both the mRNA and protein levels. To determine the function of select diet and colon carcinogen modulated miRNAs and to validate their targets, we carried out a series of loss and gain of function experiments along with luciferase reporter assays. We verified that PDE4B and TCF4 are direct targets of miR-26b and miR-203, respectively. PTK2B was determined to be an indirect target of miR-19b. In addition, microRNA physiological function was assessed by examining effects on apoptosis and cell proliferation. To better understand how the colonic stem cell population responds to environmental factors such as diet and carcinogen, we investigated the chemoprotective effects of dietary agents on miRNAs in colonic stem cells obtained from Lgr5-EGFP-IRES-creERT2 knock in mice injected with AOM. We demonstrated that based on relative expression of miR-125a-5p, miR-190b and miR-191 in stem cells vs. daughter cells and differentiated cells, these miRNAs may be stem cell specific miRNAs. We also identified miR-21 to be significantly reduced in stem cells compared to differentiated cells and selectively modulated by these dietary agents in stem cells. In summary, our results indicate for the first time that fish oil plus pectin protect against colon tumorigenesis in part by modulating a subset of miRNAs and their target genes (mRNAs) implicated in the regulation of the colon stem cell niche and tumor development

Evaluation of abnormal uterine bleeding: role of diagnostic hysteroscopy and its correlation with histopathology

Background: The objective was to assess the accuracy of diagnostic hysteroscopy in evaluation of abnormal uterine bleeding and to correlate hysteroscopic findings with histopathology reports.Methods: A prospective study was carried out at our institute from January 2010 to December 2013. Ninety cases were included in this study. Patients’ age varied from 20 to 60. Those women with the history of abnormal uterine bleeding were admitted. In all cases diagnostic hysteroscopic examination and dilatation and curettage were carried out. Endometrium was sent for histopathology and correlation of hysteroscopic findings with histopathology reports was studied.Results: Various findings on hysteroscopy are as following: proliferative endometrium 36.66%, secretary endometrium 17.77% endometrial hyperplasia 24.44%, atrophic endometrium 5.55%, endometrial polyp 8.88%, submucous fibroid 4.44%, and endometrial carcinoma 2.22%.Conclusions: Hysteroscopy is an eye in uterus and it provides more accurate diagnosis than dilatation and curettage alone in patients with abnormal uterine bleeding.

Towards a synthesis of C<SUB>3</SUB>-tribenzohemifullerene, a C<SUB>42</SUB>H<SUB>18</SUB> fragment of [60]fullerene

A short, simple synthesis of C3-trinaphthotriphenylene 6, C42H24, from readily available precursors involving threefold Wittig reactions and threefold oxidative photocyclizations is reported; flash vacuum pyrolysis of 6 in the quest for C3-tribenzohemifullerene 5, C42H18, has so far led only to the formation of monobridged product 12, C42H22

Priprava i karakterizacija čvrstih disperzija etorikoksiba s polietilenglikolom 4000 i polivinilpirolidonom K30

The objective of the present investigation was to study the influence of polyethylene glycol 4000 (PEG) and polyvinylpyrrolidone K30 (PVP) on in vitro dissolution of etoricoxib from solid dispersions. The preliminary studies were carried out using physical mixture of drug and carriers. The solid dispersions were prepared using the solvent evaporation method. A 32 factorial design was adopted in the solvent evaporation method using the concentration of PEG and PVP as independent variables. Full and reduced models were evolved for dependant variables, such as the percentage of drug release in 10 min (Q10), percentage of drug release in 30 min (Q30), percentage of drug release in 45 min (Q45) and percent dissolution efficiency (DE). The reduced models were validated using two check points. Q10 > 65%, Q30 > 75%, Q45 > 85% and DE > 80% were used as constraints for the selection of an optimized batch. Contour plots are presented for the selected dependant variables. PEG was found to be more effective in increasing the drug dissolution compared to PVP. Wettability study was carried out for pure drug and optimized batch. FT-IR spectroscopy, microscopic study, differential scanning calorimetry and X-ray diffraction study were carried out in order to characterize drug in the solid dispersions. Improved dissolution was attributed to decreased crystallinity of the drug, improved wetting and solubilizing effects of carriers such as PEG and PVP from the solid dispersion of etoricoxib. In conclusion, dissolution of etoricoxib can be modulated using appropriate levels of hydrophilic carriers.U radu je proučavan utjecaj polietilenglikola 4000 (PEG) i polivinilpirolidona K30 (PVP) na in vitro oslobađanje etorikoksiba iz čvrstih disperzija. Preliminarni pokusi provedeni su sa smjesom ljekovite tvari i polimernih nosača. Čvrste disperzije pripravljene su metodom uparavanja otapala. Za ovu metodu razvijen je 32 faktorijalni dizajn koristeći koncentraciju PEG i PVP kao nezavisne varijable. Za zavisne varijable razvijeni su potpuni i reducirani modeli, kao što su postotak oslobođene ljekovite tvari u 10 (Q10), 30 (Q30) ili 45 minuta (Q45) i postotak učinkovitosti oslobađanja (DE). Reducirani modeli su validirani pomoću dviju kontrolnih točaka. Q10 > 65%, Q30 > 80%, Q45 > 85% i DE > 80% su upotrebljeni kao ograničenja za izbor optimirane serije. Prikazane su konturne linije za pojedine zavisne varijable. Oslobađanje lijeka bilo je učinkovitije iz pripravaka s PEG-om. Vlaženje je proučavano za čistu ljekovitu supstanciju i omptimiranu seriju. Za karakterizaciju ljekovite tvari u čvrstim disperzijama korištene su FT-IR spektroskopija, mikroskopske studije, diferencijalna pretražna kalorimetrija i difrakcija rentgenskim zrakama. Povećano oslobađanje posljedica je smanjene kristaliničnosti ljekovite tvari, pojačanog vlaženja i solubilizacijskog učinka polimernih nosača u disperzijama. Može se zaključiti da se oslobađanje etorikoksiba može modulirati promjenom količine hidrofilnih nosača